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Provides information on the organization of weed research in the German Federal Republic. Reason for the lack of pattern in the organization and coordination of weed research in the country; Studies being conducted at the Institut fur Pflanzenschutz der Landwirtschaftlichen Hochschule at Hohenheim; Other centres that carry out basic and applied research on weeds.

We detected delayed and reduced antibody and T-cell responses after BNT162b2 vaccination in 71 elderly persons (median age 81 years) compared with 123 healthcare workers (median age 34 years) in Germany. These data emphasize that nonpharmaceutical interventions for coronavirus disease remain crucial and that additional immunizations for the elderly might become necessary.

One week after second vaccinations were administered, an outbreak of B.1.1.7 lineage severe acute respiratory syndrome coronavirus 2 infections occurred in a long-term care facility in Berlin, Germany, affecting 16/20 vaccinated and 4/4 unvaccinated residents. Despite considerable viral loads, vaccinated residents experienced mild symptoms and faster time to negative test results.

Background: The German NIU HER2 model was developed based on five variables found to have statistically significant influences on HER2-positivity, to allow exploration of deviations between model-predicted and actual HER2-positivity rates as a measure of testing quality. The prospective, non-interventional EPI HER2 BC study (NCT02666261) compared NIU and EPI data, aiming to validate the NIU model., Methods: HER2 status and patient-/tumour-related information were collected from eligible patients with invasive breast cancer. The influence of variables on HER2-positivity was compared between studies and the NIU model validated using EPI data with cut-off and variable coefficients from the NIU study. The influences of additional variables, centre effects and laboratory-specific parameters were also explored., Results: The study included 14,729 EPI and 15,281 NIU samples; HER2-positivity rates were comparable (13.5% versus 14.2%). The five covariates from NIU were shown to significantly affect HER2-positivity using EPI data. The Youden Index for the NIU model refitted to EPI data (0.3632) and the NIU model for prediction of HER2-positivity in EPI (0.3552) was close to that for the NIU model fitted to NIU data (0.3888), validating the NIU model. Replacing hormone receptor status with progesterone and oestrogen receptor expression, and adding method of sample extraction as a variable improved the model's predictive strength (ROC AUC 0.7402; Youden Index 0.3935)., Conclusions: Reliable, high-quality HER2-testing methods are essential for selection of patients with HER2-positive breast cancer for HER2-tageted treatment. Integration of our model into a locally used software or website may improve its viability for use in clinical practice., Competing Interests: Declaration of competing interest All authors received support for third-party writing assistance for this manuscript, provided by Roche Pharma AG, Grenzach-Wyhlen, Germany. J.R. received a grant and non-financial support from Roche Pharma AG during the conduct of this study. A.L. received a grant from Roche Pharma AG during the conduct of this study, and received travel fees from Roche, Novartis and BioNTech Diagnostics, and grants from BioNTech Diagnostics, outside the submitted work. P.S. received a grant and personal fees from Roche Pharma AG during the conduct of this study, and received grants and personal fees from Roche and Genomic Health, and personal fees from Novartis, outside the submitted work. H.-U.S. is an employee of Targos Molecular Pathology (Kassel, Germany) and received personal fees for consulting from Roche during the conduct of this study and from BMS, MSD, Novartis Oncology, Pfizer and Abbott Molecular outside the submitted work. T.D. received travel and consulting fees from Leica Biosystems, Inc. J.A. and C.K. are employees of Roche and have stock ownership in Roche. W.K. is an employee of BDS Koch, which receives fees from Roche and other clients for statistical services. M.U. has received personal fees and non-financial support from AbbVie, Amgen GmbH, AstraZeneca, Celgene GmbH, Daiichi Sankyo, Eisai GmbH, Janssen Cilag, Johnson & Johnson, Lilly Int., MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer GmbH, Riemser, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, Sividon Diagnostics and TEVA Pharmaceuticals Industries Ltd, and personal fees from BMS, Lilly Deutschland and PUMA Biotechnology, outside the submitted work., (Copyright © 2019. Published by Elsevier Ltd.)

HER2 testing in metastatic gastric or gastroesophageal junction cancer (mGC/mGEJC) is standard practice. Variations in HER2-positivity rates suggest factors affecting test quality; however, the influence of patient-, tumor-, and laboratory-related factors on HER2-positivity rates remains unknown. This observational, prospective study collected routine HER2 testing data from 50 pathology centers in Germany (January 2013-December 2015). For each sample, HER2 status, primary tumor location, method of sample retrieval, and other patient- and tumor-related parameters were recorded. A model for predicting the probability of HER2-positivity was developed using stepwise multiple logistic regression to identify influencing factors. Documented positivity rates and corresponding predicted HER2-positivity probabilities were compared to identify institutes with deviations in HER2-positivity. Data from 2761 mGC/mGEJC routine diagnostic specimens included 2033 with HER2 test results (1554 mGC, 479 mGEJC); overall HER2-positivity rates across centers were 19.8% and 30.5%, respectively. HER2-positivity correlated most with Lauren classification, then HER2 testing rate, primary tumor location, sample type, and testing method (all p < 0.05). Three institutes had model-predicted HER2-positivity rates outside the 95% confidence interval of their documented rate, which could not be explained by sample and center characteristics. Results demonstrated the high quality of routine HER2 testing in the mGC/mGEJC cohort analyzed. This is the first study investigating parameters impacting on HER2-positivity rates in mGC/mGEJC in routine practice and suggests that assessment of HER2 testing quality should consider primary tumor location, testing method and rate, and tumor characteristics. Accurate identification of patients with HER2-positive mGC/mGEJC is essential for appropriate use of HER2-targeted therapies.

Quality control of BRAF mutation testing methods used in routine practice is crucial for optimal treatment selection. In this prospective study, we assessed the impact of patient/sample characteristics on BRAF mutation testing results in patients with melanoma, during clinical practice. Data were collected on routine testing practices and documented mutation status in patients with melanoma stages IIIB, IIIC, or IV across 28 diagnostic pathology centers in Germany. Patient/sample data collected included: patient age, location of primary melanoma and metastases, origin of sample, melanoma subtype, and quality of tissue. Statistical influence of patient/sample characteristics on BRAF mutation rate was assessed using multiple logistic regression analyses and statistical models developed to predict the probability of BRAF mutations for individual patient cohorts. Data/samples from 642 patients with melanoma were analyzed. BRAF mutations were documented in 241/642 patients (37.5%). The primary statistical model to predict BRAF mutation rates included: age (continuous), origin of sample, method of mutation analysis, and quality of tissue. Analyses of post hoc collected data identified major deviations between documented mutation rates included in this study vs. routinely recorded mutation rates for three centers. When samples from these centers were excluded, the influence of testing method was no longer statistically significant. The final model included patient age, origin of sample (including metastasis location), and quality of tissue. Once validated in an independent population, this type of model could allow pathology centers to compare the performance of their testing methods with what would be expected based on patient, tumor, and sample characteristics.

In a genome-wide scan, isolated single nucleotide polymorphisms (SNPs), including rs17465637, in the melanoma inhibitory activity 3 gene (MIA3) on chromosome 1 were identified to be associated with coronary artery disease and myocardial infarction (MI). Because the role of common variation at the MIA3 locus has not yet been investigated, the aim of this case-control study was to determine the impact of haplotype-tagging SNPs and haplotypes in the MIA3 region on the risk of MI. In a set of nine haplotype-tagging SNPs, rs17465637, but none of the other SNPs, was associated with MI. After adjustments were made for age, gender, history of arterial hypertension, history of hypercholesterolaemia, current cigarette smoking and diabetes mellitus, multiple logistic regression analyses showed an increased risk in the carriers of one or two C alleles [adjusted odds ratio (OR) 1.17, 95% confidence interval (CI) 1.04-1.32, and 1.37, 95% CI 1.08-1.74, respectively]. Nine common haplotypes (frequency >1%) were established across the MIA3 region. Two of the haplotypes were associated with an increased risk of MI: the frequent (48%) TGACCAAAG haplotype and the rare (2%) CGACCAAAG haplotype (adjusted OR 1.102, 95% CI 1.002-1.212, and 1.574, 95% CI 1.077-2.298, respectively). Showing association between rs17465637 and MI, this work was consistent with results from the original detection study and most prior replication studies addressing this issue. In addition to correspond with such isolated evidence of association with MI, the present study identified specific haplotypes capturing the risk-related variation in the entire MIA3 region.

Background and Purpose: Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data., Methods: Four intravenous dose regimens (total cumulative doses of 30-180 μg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch., Results: Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³., Conclusions: We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.

We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p 1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99-1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00-1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis.

Purpose: Haplotypes based on polymorphisms in the gene encoding 5-lipoxygenase-activating protein have been linked with susceptibility to myocardial infarction in Iceland and the United Kingdom. We sought to replicate these association findings in a large case-control sample from Germany., Methods: The case group included 3657 patients with myocardial infarction and the control group comprised 1211 individuals with angiographically normal coronary arteries and without clinical signs or symptoms of myocardial infarction. Nine different polymorphisms were genotyped with the use of the TaqMan technique., Results: Genotype, allele, and haplotype analyses did not reveal significant associations between the polymorphisms and myocardial infarction. The negative results included a four-marker haplotype, termed HapA haplotype (odds ratio = 1.10; 95% confidence interval: 0.96-1.25), that was previously found to be related with myocardial infarction in a sample from Iceland, and a different four-marker haplotype, termed HapB haplotype (odds ratio = 0.94; 95% CI: 0.79-1.12), that was previously linked with myocardial infarction in a sample from the United Kingdom. Nine-marker haplotypes were not significantly associated with myocardial infarction in multiple logistic regression models adjusted for covariates (P >or= 0.38)., Conclusion: In this sample from central Europe, specific polymorphisms in the gene for 5-lipoxygenase-activating protein were not associated with myocardial infarction, a result contrasting previous positive findings.

Background: Little evidence exists on the role of homocysteine as a predictor of mortality in patients with type 2 diabetes. The aim of this study was to investigate whether elevated plasma homocysteine levels are independently associated with all-cause or cardiovascular mortality in patients with type 2 diabetes and coronary artery disease., Methods: This is a prospective cohort study that included 507 patients with type 2 diabetes and angiographically proven coronary artery disease. Patients were divided into 2 groups according to homocysteine level above or below median value (12.4 micromol/L): the high homocysteine group (255 patients) and the low homocysteine group (252 patients). The primary end-point of the study was all-cause mortality., Results: There were 103 deaths during a 4-year follow-up: 62 deaths in the high homocysteine group and 41 deaths in the low homocysteine group (Kaplan-Meier estimates of mortality 25.6% and 17.4%, respectively (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.03-2.27, P=0.031). Sixty-two of 103 deaths (60.2%) were of cardiovascular origin: 37 deaths (14.5%) occurred in the high homocysteine group and 25 deaths (9.9%) occurred in the low homocysteine group (P=0.115). Cox proportional hazards model showed that plasma homocysteine was not an independent correlate of all-cause (adjusted hazard ratio [HR] 1.10, 95% CI 0.89-1.33; P=0.397 for 5 micromol/L increase in concentration) or cardiovascular (adjusted HR 1.04, 95% CI 0.80-1.36, P=0.753, for 5 micromol/L increase in concentration) mortality., Conclusion: In patients with type 2 diabetes and coronary artery disease, elevated level of homocysteine is an associate of increased cardiovascular risk but not an independent predictor of cardiovascular mortality.

Objective: There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still's disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility., Material and Methods: For association analysis, 470 patients with Crohn's disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system., Results: When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p=0.089 and p=0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p=0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p=0.53 and p=0.79, respectively)., Conclusion: The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.

Background: The effects of estrogen on blood vessels are partly due to changes in vascular cell gene expression and protein synthesis that are mediated by estrogen receptors. In previous association studies, the -397T/C (rs2234693) and -351A/G (rs9340799) single nucleotide polymorphisms in the estrogen receptor alpha gene (ESR1) have been implicated in the risk of coronary atherosclerosis and myocardial infarction. To test these findings, we examined the relationship of the polymorphisms to myocardial infarction in a large sample of white patients and control individuals of predominantly European descent., Methods and Results: The case group included 3657 patients with myocardial infarction, and the control group comprised 1211 individuals with angiographically normal coronary arteries and without signs or symptoms of myocardial infarction. TaqMan assays were used for the determination of genotypes. Genotype distributions of the -397T/C and -351A/G polymorphisms were not significantly different between the control and patient groups (P> or =0.85). The frequencies of haplotypes defined by the -397T/C and -351A/G polymorphisms were similar in the control group and the patient group (P=0.42). In addition, the distributions of haplotype-defined genotypes (diplotypes) were not significantly different between the control group and the patient group (P=0.81). Separate analyses in women and men did not reveal sex-related associations of specific genotypes or haplotypes of the polymorphisms with myocardial infarction (P> or =0.25)., Conclusions: The results indicate that the -397T/C and -351A/G polymorphisms of ESR1 or haplotypes based on these polymorphisms are not associated with myocardial infarction in a white population.

Aim: The lately updated German guideline on radiation protection in medicine (Richtlinie Strahlenschutz in der Medizin) requires the physician who administers radioactive substances for therapy, to perform and document follow-ups. In order to decrease the administrative burden, an electronic database was developed that interfaces with a word processing software to generate written reports and statistic analysis., Methods: Based on Microsoft Access and Microsoft Visual Basic a database was created to monitor patients with benign and malignant thyroid disorders after radioiodine therapy. It permits automatic creation of therapy documents and necessary patient reports in Microsoft Word. Intuitive handling, third level of normalization in database architecture and automatic plausibility checks guarantee integrity of the data and the efficacy of the database., Results, Conclusion: The new software has been a success in over 1500 patients and over 3800 in- and outpatient therapies and visits. The effort of data entry is easily offset by the automatic generation of the necessary patient reports. The required supervision of the follow-up appointments is now also user-friendly and efficient.

Single nucleotide polymorphisms (SNPs) in the human genome are thought to be organised into blocks of high internal linkage disequilibrium (LD), separated by intermittent recombination hotspots. Since understanding haplotype structure is critical for an accurate assessment of inter-individual genetic differences, we investigated up to 968 SNPs from a 10-Mb region on chromosome 6p21, including the human major histocompatibility complex (MHC), in five different population samples (45-550 individuals). Regions of well-defined block structure were found to coexist alongside large areas lacking any clear structure; occasional long-range LD was observed in all five samples. The four white populations analysed were remarkably similar in terms of the extend and spatial distribution of local LD. In US African Americans, the distribution of LD was similar to that in the white populations but the observed haplotype diversity was higher. The existence of large regions without any clear block structure renders the systematic and thorough construction of SNP haplotype maps a crucial prerequisite for disease-association studies.